The overall objectives of this research proposal are (1) the elucidation of some important factors which determine graft immunogenicity (the capacity of grafts to evoke specific transplantation immunity), and (2) the evaluation of whether graft immunogenicity can be significantly modified so as to promote graft survival and function. For the latter, we will use two transplant systems, naturally vascularized neonatal heart tissue allografts in inbred mice and surgically anastomosed adult heart organ allografts in inbred rats, to carefully and systematically screen the capacity of a variety of physical, chemical, and biological agents to reduce graft immunogenicity and prolong graft survival by treatment of grafts in vitro just prior to transplantation. For the former, we will test and compare the immunogenicity and susceptibility to rejection of a variety of tissue and organ allografts in inbred mice and rats under a variety of experimental conditions. Moreover, we will undertake critical experiments to determine the importance of passenger leukocytes, tissue specific histocompatibility antigens, graft "adaptation" and serum- blocking factors in graft immunogenicity.